Ammonia → 2-Methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzamide

Participants

Reaction Steps

(R)-2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid (Example 9-1; 1.026 g, 2.10 mmol) was dissolved in 20 mL CH2Cl2 and treated with oxalyl chloride (0.22 mL, 2.52 mmol) and 10 mL of dimethyl formamide. The mixture was allowed to stir for 1 h until all solids had dissolved. 10 mL of THF saturated with ammonia was added slowly. A thick white precipitate formed. The slurry was stirred for 20 min then diluted with diethyl ether (100 mL), washed with 100 mL of each of H2O, 0.2 N aqueous HCl, saturated aqueous NaHCO3, and brine. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was flash chromatographed with 50% ethyl acetate/hexanes to yield 740 mg (72%) of the desired 2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzamide as a clear oil.

Provenance & Evidence